title: In vitro cytotoxicity of melleolide antibiotics: structural and mechanistic aspects.
abstract: Melleolide sesquiterpene aryl esters are secondary products of the mushroom genus Armillaria. We compared the cytotoxicity of eleven melleolides--five thereof are new natural products--against four human cancer cell lines. Armillaridin, 4-O-methylarmillaridin, and dehydroarmillylorsellinate were most active, at IC(50) = 3.0, 4.1 and 5.0 μM, respectively, against Jurkat T cells for the former two compounds, and K-562 cells for the latter. Dehydroarmillylorsellinate did not inhibit respiration and RNA-synthesis of K-562 cells at 5 μM. However, replication of DNA dropped to 35% after 120 min at this concentration, and translational activity also decreased.
authors.affiliation: Department Pharmaceutical Biology, Friedrich-Schiller-Universität Jena, Hans-Knöll-Institute, Beutenbergstrasse 11a, 07745 Jena, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bohnert
authors.forename: Sebastian
authors.initials: S
authors.lastname: Miethbauer
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Dahse
authors.forename: Johannes
authors.initials: J
authors.lastname: Ziemen
authors.forename: Markus
authors.initials: M
authors.lastname: Nett
authors.forename: Dirk
authors.initials: D
authors.lastname: Hoffmeister
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001487:Basidiomycota / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012459:Salicylates / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D012459:Salicylates; D012717:Sesquiterpenes; D004247:DNA